CN117800867A - Improved pretilachlor preparation method - Google Patents
Improved pretilachlor preparation method Download PDFInfo
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- CN117800867A CN117800867A CN202311653363.0A CN202311653363A CN117800867A CN 117800867 A CN117800867 A CN 117800867A CN 202311653363 A CN202311653363 A CN 202311653363A CN 117800867 A CN117800867 A CN 117800867A
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- YLPGTOIOYRQOHV-UHFFFAOYSA-N Pretilachlor Chemical compound CCCOCCN(C(=O)CCl)C1=C(CC)C=CC=C1CC YLPGTOIOYRQOHV-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 239000012535 impurity Substances 0.000 claims abstract description 65
- 238000004945 emulsification Methods 0.000 claims abstract description 17
- 239000012043 crude product Substances 0.000 claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims description 33
- 238000000034 method Methods 0.000 claims description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 20
- DTEGEQGTAYAXBC-UHFFFAOYSA-N 2,6-diethyl-n-(2-propoxyethyl)aniline Chemical compound CCCOCCNC1=C(CC)C=CC=C1CC DTEGEQGTAYAXBC-UHFFFAOYSA-N 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 12
- 239000003054 catalyst Substances 0.000 claims description 10
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 claims description 9
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 229910052763 palladium Inorganic materials 0.000 claims description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 3
- 150000007522 mineralic acids Chemical class 0.000 claims description 3
- 229910052697 platinum Inorganic materials 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 239000012074 organic phase Substances 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 239000001257 hydrogen Substances 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 7
- 239000012071 phase Substances 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 230000001804 emulsifying effect Effects 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- FOYHNROGBXVLLX-UHFFFAOYSA-N 2,6-diethylaniline Chemical compound CCC1=CC=CC(CC)=C1N FOYHNROGBXVLLX-UHFFFAOYSA-N 0.000 description 4
- YEYKMVJDLWJFOA-UHFFFAOYSA-N 2-propoxyethanol Chemical compound CCCOCCO YEYKMVJDLWJFOA-UHFFFAOYSA-N 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 238000004817 gas chromatography Methods 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- 238000010606 normalization Methods 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- ZTSNTGUKFJYLKX-UHFFFAOYSA-N N,2,6-triethyl-N-propoxyaniline Chemical compound O(CCC)N(C1=C(C=CC=C1CC)CC)CC ZTSNTGUKFJYLKX-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000001276 controlling effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000006561 solvent free reaction Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- VONWPEXRCLHKRJ-UHFFFAOYSA-N 2-chloro-n-phenylacetamide Chemical compound ClCC(=O)NC1=CC=CC=C1 VONWPEXRCLHKRJ-UHFFFAOYSA-N 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 241000192043 Echinochloa Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 239000012159 carrier gas Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000009834 vaporization Methods 0.000 description 1
- 230000008016 vaporization Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/22—Separation; Purification; Stabilisation; Use of additives
- C07C231/24—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to an improved pretilachlor preparation method, which is characterized in that after a pretilachlor crude product is obtained, the following impurity 1 in a system is removed to eliminate emulsification:
Description
Technical Field
The invention relates to an improved pretilachlor preparation method.
Background
The pretilachlor belongs to 2-chloracetanilide, is a special bud-phase herbicide with high selectivity for paddy fields, can prevent and remove weeds such as barnyard grass, ox felt and the like in the paddy fields, and has wide application.
The current pretilachlor production process is widely adopted as follows: 2, 6-diethyl aniline and ethylene glycol monopropyl ether react under the action of a catalyst to obtain an intermediate N-propoxyl ethyl-2, 6-diethyl aniline shown in the formula (1), and then the intermediate N-propoxyl ethyl-2, 6-diethyl aniline reacts with chloroacetyl chloride to obtain pretilachlor shown in the formula (2).
It has been reported that the intermediate N-propoxyethyl-2, 6-diethylaniline of formula (1) can be synthesized in one step by the following route (see, for example, U.S. Pat. Nos. 4183868 and 4921980):
disclosure of Invention
When the inventor of the present application produced pretilachlor by the above method, it was found that the emulsification occurred in the reaction system in the pretilachlor synthesis step, and particularly when this step was a solvent-free reaction, the emulsification was more serious, affecting the post-treatment of the product.
The inventors tried various demulsification measures, for example, emulsification was eliminated by standing for 1 to 2 days, but such long standing resulted in low production efficiency; emulsification can be eliminated by adding a large amount of solvent, but this treatment method causes solvent residue, and the use of a large amount of solvent increases production cost and increases environmental burden.
In order to better solve the above emulsification problem, the present inventors have conducted intensive studies on the cause of emulsification, and found that emulsification may be associated with impurities generated in the synthesis step of N-propoxyethyl-2, 6-diethylaniline. Based on this idea, the inventors of the present application studied about impurities in a reaction system and a method for eliminating the same, and as a result, found that emulsification can be eliminated by adding an acid to the reaction system after the pretilachlor synthesis step to adjust the pH of the system to be acidic.
Specifically, the present invention provides:
(1) An improved pretilachlor preparation method is characterized in that after a pretilachlor crude product is obtained, the following impurity 1 in a system is removed to eliminate emulsification:
(2) The method of the above (1), wherein the pH of the system is adjusted to 6 or less, preferably to a pH of 1 to 3 by adding an acid to the system, thereby removing the impurity 1 and eliminating emulsification.
(3) The method of the above (1) or (2), wherein the crude pretilachlor is prepared by the following reaction steps:
step one:
step two:
(4) The method according to the above (2), wherein the reaction in the second step is carried out under solvent-free conditions.
(5) The method according to any one of the above (1) to (4), wherein any one or both of the following impurity 2 and impurity 3 are also removed by adding an acid:
(6) The method according to any one of the above (1) to (5), wherein any one or both of the following impurities 4 and 5 are also removed by adding an acid:
(7) The method according to any one of the above (1) to (6), wherein the acid is an inorganic acid, preferably hydrochloric acid, sulfuric acid or phosphoric acid, preferably hydrochloric acid.
(8) The process according to any one of the above (1) to (7), wherein the chloroacetyl chloride in the step (II) is 0.98 to 1.05 molar equivalents of the intermediate N-propoxyethyl-2, 6-diethylaniline represented by the formula (1).
(9) The process according to any one of the above (1) to (8), wherein the catalyst in the step one is a catalyst containing 0.05 to 10% of palladium (Pd) or 0.2 to 10% of platinum (Pt).
Detailed Description
The invention relates to an improved pretilachlor preparation method, which is characterized in that after a pretilachlor crude product is obtained, acid is added into a system to adjust the pH of the system to be less than 6, and the pH is preferably 1-3.
The applicant of the present invention has found that the crude pretilachlor product prepared by known methods (for example, U.S. Pat. nos. 4183868 and 4921980) comprises the following impurities:
among these impurities, impurity 1 and impurity 2 are new impurities which have not been reported and have been found for the first time by the inventors of the present application. In particular impurity 1, the inventors have found that it is a hydrophilic, lipophilic, amphiphilic substance, highly correlated with emulsification.
Therefore, the invention adds acid into the reaction system after the pretilachlor crude product is obtained, so that the pretilachlor is converted into salt and enters into the water phase, and the target product pretilachlor is remained in the organic phase, thereby eliminating emulsification, leading the water phase and the organic phase in the reaction system to be smoothly layered, and being convenient for the separation and the post-treatment of pretilachlor products.
Although the above impurities are mainly produced in the step of preparing the intermediate N-propoxyethyl-2, 6-diethylaniline represented by the formula (1), the inventors of the present application have not chosen to remove these impurities by adding an acid immediately after this step, since the intermediate N-propoxyethyl-2, 6-diethylaniline represented by the formula (1) itself is also an amine, and if an acid is added at this stage, it is largely lost.
In some embodiments, the pH of the system is adjusted to 1-6, preferably 1-3, with an acid, whereby the impurities are sufficiently salted with the acid to dissolve in the aqueous phase, thereby achieving a demulsifying effect. When the pH is more than 6, the impurities cannot be completely salified, and the demulsification is insufficient.
In some embodiments, the acid is an inorganic acid such as hydrochloric acid, sulfuric acid, or phosphoric acid, preferably hydrochloric acid.
In the present invention, the crude pretilachlor can be prepared by, for example, the following reaction steps:
step one:
step two:
in some embodiments, the catalyst in the first step is a catalyst containing 0.05-10% palladium (Pd) or 0.2-10% platinum (Pt), and the reaction temperature is 190-270 ℃, and the reaction pressure is 1-2 atm, and the catalyst is performed under the condition of no solvent.
In some embodiments, the reaction of step two is performed in the absence of a solvent. In solvent-free reaction systems, the emulsification is more severe. Thus, the demulsification method of the present invention can be preferably applied to such a solvent-free reaction system.
In other embodiments, the chloroacetyl chloride in step two is 0.98 to 1.05 molar equivalents of the intermediate N-propoxyethyl-2, 6-diethylaniline of formula (1) to ensure that the N-propoxyethyl-2, 6-diethylaniline is fully reacted.
Examples
The process according to the invention is described in detail below with reference to specific examples.
In the examples and comparative examples of the present application, detection conditions by gas chromatography were as follows:
gas phase test conditions: instrument: SP-2100A gas chromatograph, hydrogen flame ionization detector; chromatographic column: length 30m, inner diameter 0.32mm; fixing solution: SE-54 weak polarity column; microsyringe: 1 μl; column temperature: after being kept at 90 ℃ for 3.5min, the temperature is increased to 280 ℃ at a speed of 20 ℃/min and kept for 25min; vaporization chamber temperature: 290 ℃; detector temperature: 290 ℃; carrier gas: nitrogen gas; nitrogen pressure: 0.08MPa; hydrogen pressure: 0.2MPa; air pressure: 0.2MPa.
Example 1 preparation of intermediate N-propoxyethyl-2, 6-diethylaniline
A catalyst containing 5% of palladium (Pd) is adopted, 40g of the catalyst is added into a 1L reaction kettle, hydrogen is introduced into the reaction kettle for reduction and activation for 1 hour at 200 ℃, 104.2g of ethylene glycol monopropyl ether (1.0 mol) and 298.5g of 2, 6-diethylaniline (2.0 mol) are added, the reaction temperature is 190-200 ℃, the reaction pressure is 1-2 atm, and the reaction time is 4 hours, thus obtaining a crude product. The reaction crude product (excluding water) contained 15.3% ethylene glycol monopropyl ether (peak relative retention time 4.0 min) and 30.0% 2, 6-diethylaniline (peak relative retention time 10.5 min), 50.7% N-propoxyethyl-2, 6-diethylaniline (peak relative retention time 12.6 min), 4.0% other impurities, as measured by the above gas chromatography normalization method.
Separating the crude product in a separating funnel, discarding a water layer, then placing an organic layer in a 500mL three-port bottle, carrying out reduced pressure rectification under the pressure of-0.095 to-0.098 MPa, setting the reflux ratio to be 4:1, controlling the temperature to be 190-200 ℃, rectifying to obtain raw materials such as ethylene glycol monopropyl ether, 2, 6-diethylaniline and the like, controlling the temperature to be 200-240 ℃, and continuing to rectify to obtain an intermediate N-propoxyethyl-2, 6-diethylaniline. The area normalization content of the N-propoxyl ethyl-2, 6-diethylaniline is 96.7% by adopting the gas chromatography normalization method.
Detecting an intermediate N-propoxyethyl-2, 6-diethylaniline by adopting the gas chromatography normalization method, and determining the molecular weight by using a gas chromatograph-mass spectrometer, wherein the peak-out relative retention time of main impurities is respectively as follows:
10.7 min (MS-ESI (m/z): 151.13[ M+H ]] + Impurity 5);
11.5 min (MS-ESI (m/z): 192.17[ M+H)] + Impurity 4);
13.6 min (MS-ESI (m/z): 264.28[ M+H)] + Impurity 3);
14.1 min (MS-ESI (m/z): 278.31[ M+H ]] + Impurity 2);
15.2 min (MS-ESI (m/z): 280.26[ M+H)] + Impurity 1).
And (3) rectifying the intermediate, controlling the pressure to be-0.095 to-0.098 MPa and the reflux ratio to be 10:1, gradually heating and rectifying from 200 ℃, collecting fractions with the content of the three impurities being more than 5%, and separating by the following preparation chromatography conditions.
Detection conditions for preparative chromatography: the chromatographic column adopts a C18 column, the diameter is 30mm, the length is 250mm, and the particle size of the filling material is 10um; the mobile phase is acetonitrile: water (0.1% by weight of ammonium acetate in water) =80:20; the flow rate is 40mL/min; the detection wavelength was 280nm.
In the preparation chromatography, impurities 1-3 with the content of more than 95% are respectively obtained, and are detected through a hydrogen spectrum:
hydrogen spectrum of impurity 1 at 15.2 min: 1 HNMR(400MHz,DMSO)δ6.96(brd,J＝7.5Hz,2H),δ6.84(dd,J＝7.1,8.0Hz,1H),δ3.73(brm,2H),δ3.51(m,6H),δ3.35(t,J＝6.6Hz,2H),δ3.01(m,2H),δ2.61(q,J＝7.6Hz,4H),δ1.50(m,2H),δ1.15(t,J＝7.6Hz,6H),δ0.86(t,J＝7.4Hz,3H)。
hydrogen spectrum of impurity 2at 14.1 min: 1 HNMR(400MHz,DMSO)δ7.05(m，3H),δ3.34(t,J＝6.2Hz,2H),δ3.27(t,J＝6.5Hz,2H),δ3.11(t,J＝6.2Hz,2H),δ2.94(m,2H),δ2.66(q,J＝7.6Hz,4H),δ1.47(m,2H),δ1.38(m,2H)δ1.15(t,J＝7.6Hz,6H),δ0.84(t,J＝7.4Hz,3H),δ0.79(t,J＝7.3Hz,3H)。
hydrogen spectrum of impurity 3 at 13.6 min: 1 HNMR(400MHz,DMSO)δ7.05(m，3H),δ3.34(t,J＝6.2Hz,2H),δ3.27(t,J＝6.5Hz,2H),δ3.11(t,J＝6.2Hz,2H),δ3.05(q,J＝7.1Hz,2H),δ2.66(q,J＝7.5Hz,4H),δ1.47(m,2H),δ1.15(t,J＝7.5Hz,6H),δ0.95(t,J＝7.1Hz,3H),δ0.84(t,J＝7.4Hz,3H)。
the N-propoxyethyl-2, 6-diethylaniline used in the following examples and comparative examples was 96.7% in which the content of impurity 1 was 0.94%, the content of impurity 2 was 0.65%, the content of impurity 3 was 0.88%, the content of impurity 4 was 0.3% and the content of impurity 5 was 0.23%.
Example 2
106.4. 106.4g N-propoxyethyl-2, 6-diethylaniline (0.437 mol) and 130g of 23% Na 2 CO 3 Adding the aqueous solution (0.283 mol) into a reaction bottle, dropwise adding 50.3g of chloroacetyl chloride (0.446 mol) in 1h at 30-40 ℃, continuing to react for 1h after the dropwise adding is finished, tracking until the reaction of the raw materials is within the residual 1.0%, obviously emulsifying a reaction system, regulating the pH to 6 by hydrochloric acid, starting to slowly layer, standing for about 2h, separating liquid, discarding the aqueous phase, detecting an organic phase, wherein the impurity 1 content is 0.34%, the impurity 2 content is 0.32%, the impurity 3 content is 0.37%, the impurity 4 content is 0.02% and the impurity 5 content is 0.02%. The organic phase is washed with 50g of water, and then the residual water is distilled off by a rotary evaporator at the temperature of less than or equal to 80 ℃ until the water content is less than 0.3%, so that the pretilachlor product with the content of 97.5% is obtained.
Example 3
106.4. 106.4g N-propoxyethyl-2, 6-diethylaniline (0.437 mol) and 130g of 23% Na 2 CO 3 Adding the aqueous solution (0.283 mol) into a reaction bottle, dropwise adding 50.3g of chloroacetyl chloride (0.446 mol) in 1h at 30-40 ℃, continuing to react for 1h after the dropwise adding is finished, tracking until the residual content of the raw material reaction is within 1.0%, obviously emulsifying a reaction system, regulating the pH value to 3 by hydrochloric acid, immediately starting layering, standing for about 10min, separating liquid, discarding the aqueous phase, detecting an organic phase, wherein the impurity 1 content is 0.04%, the impurity 2 content is 0.03%, the impurity 3 content is 0.04%, the impurity 4 content is 0.01% and the impurity 5 content is 0.01%. The organic phase is washed with 50g of water, and the residual water is distilled off by a rotary evaporator at the temperature of less than or equal to 80 ℃ until the water content is less than 0.3%, so that the pretilachlor product with the content of 98.3% is obtained.
Example 4
106.4. 106.4g N-propoxyethyl-2, 6-diethylaniline (0.437 mol) and 130g of 23% Na 2 CO 3 Adding the aqueous solution (0.283 mol) into a reaction bottle, and dripping at 30-40 ℃ for 1h50.3g of chloroacetyl chloride (0.446 mol), continuing to react for 1h after the dripping is finished, tracking until the reaction residual of the raw materials is within 1.0%, obviously emulsifying a reaction system, regulating the pH to be 1 by hydrochloric acid, immediately starting layering, standing for about 10min, separating liquid, discarding a water phase, detecting an organic phase, wherein the impurity 1 content is 0.03%, the impurity 2 content is 0.02%, the impurity 3 content is 0.03%, the impurity 4 content is 0.01% and the impurity 5 content is 0.01%. The organic phase is washed with 50g of water, and then the residual water is distilled off by a rotary evaporator at the temperature of less than or equal to 80 ℃ until the water content is less than 0.3%, so that the pretilachlor product with the content of 98.4% is obtained.
Comparative example 1
106.4. 106.4g N-propoxyethyl-2, 6-diethylaniline (0.437 mol) and 130g of 23% Na 2 CO 3 Adding the aqueous solution (0.283 mol) into a reaction bottle, dropwise adding 50.3g of chloroacetyl chloride (0.446 mol) in 1h at 30-40 ℃, continuing to react for 1h after the dropwise adding is finished, tracking until the reaction of the raw materials is within the residual 1.0%, obviously emulsifying the reaction system, standing for about 24h, separating liquid, discarding the aqueous phase, detecting the organic phase, wherein the impurity 1 content is 0.79%, the impurity 2 content is 0.64%, the impurity 3 content is 0.84%, the impurity 4 content is 0.1% and the impurity 5 content is 0.1%. The organic phase is washed with 50g of water, and then the residual water is distilled off by a rotary evaporator at the temperature of less than or equal to 80 ℃ until the water content is less than 0.3%, so that the pretilachlor product with the content of 96.0% is obtained.
Comparative example 2
106.4. 106.4g N-propoxyethyl-2, 6-diethylaniline (0.437 mol) and 130g of 23% Na 2 CO 3 Adding the aqueous solution (0.283 mol) into a reaction bottle, dropwise adding 50.3g of chloroacetyl chloride (0.446 mol) in 1h at 30-40 ℃, continuing to react for 1h after the dropwise adding is finished, tracking until the residual content of the raw material reaction is within 1.0%, obviously emulsifying the reaction system, regulating the pH to 7 by hydrochloric acid, standing for about 20h without emulsification improvement, separating liquid, discarding the aqueous phase, detecting an organic phase, wherein the impurity 1 content is 0.75%, the impurity 2 content is 0.62%, the impurity 3 content is 0.81%, the impurity 4 content is 0.1% and the impurity 5 content is 0.1%. The organic phase is washed with 50g of water, and then the residual water is distilled off by a rotary evaporator at the temperature of less than or equal to 80 ℃ until the water content is less than 0.3%, so that the pretilachlor product with the content of 96.1% is obtained.
Claims (9)
1. The improved pretilachlor preparation method is characterized in that after a pretilachlor crude product is obtained, the following impurity 1 in a system is removed to eliminate emulsification:
2. a process according to claim 1, wherein impurity 1 is removed and emulsification is eliminated by adding an acid to the system to adjust the pH of the system to below 6, preferably to a pH of 1-3.
3. The method according to claim 1 or 2, wherein the crude pretilachlor is prepared by the following reaction steps:
step one:
step two:
4. the process of claim 2, wherein the reaction of step two is conducted in the absence of a solvent.
5. The method according to any one of claims 1 to 4, wherein either or both of the following impurity 2 and impurity 3 are also removed by adding an acid:
6. the method according to any one of claims 1 to 5, wherein either or both of the following impurities 4 and 5 are also removed by adding an acid:
7. the process according to any one of claims 1 to 6, wherein the acid is an inorganic acid, preferably hydrochloric acid, sulfuric acid or phosphoric acid, more preferably hydrochloric acid.
8. The process according to any one of claims 1 to 7, wherein the chloroacetyl chloride in the step (ii) is 0.98 to 1.05 molar equivalents of the intermediate N-propoxyethyl-2, 6-diethylaniline represented by the formula (1).
9. The process according to any one of claims 1 to 8, wherein the catalyst in step one is a catalyst comprising 0.05 to 10% palladium (Pd) or 0.2 to 10% platinum (Pt).
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| CN202311653363.0A CN117800867A (en) | 2023-12-05 | 2023-12-05 | Improved pretilachlor preparation method |
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| CN202311653363.0A CN117800867A (en) | 2023-12-05 | 2023-12-05 | Improved pretilachlor preparation method |
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